Drosophila 14-3-3/PAR-5 is an essential mediator of PAR-1 function in axis formation

Dev Cell. 2002 Nov;3(5):659-71. doi: 10.1016/s1534-5807(02)00320-9.

Abstract

PAR-1 kinases are required to determine the anterior-posterior (A-P) axis in C. elegans and Drosophila, but little is known about their molecular function. We identified 14-3-3 proteins as Drosophila PAR-1 interactors and show that PAR-1 binds a domain of 14-3-3 distinct from the phosphoserine binding pocket. PAR-1 kinases phosphorylate proteins to generate 14-3-3 binding sites and may therefore directly deliver 14-3-3 to these targets. 14-3-3 mutants display identical phenotypes to par-1 mutants in oocyte determination and the polarization of the A-P axis. Together, these results indicate that PAR-1's function is mediated by the binding of 14-3-3 to its substrates. The C. elegans 14-3-3 protein, PAR-5, is also required for A-P polarization, suggesting that this is a conserved mechanism by which PAR-1 establishes cellular asymmetries.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 14-3-3 Proteins
  • Animals
  • Axis, Cervical Vertebra / physiology
  • Binding Sites
  • Caenorhabditis elegans Proteins*
  • Cell Polarity
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism
  • Drosophila melanogaster / physiology
  • Female
  • Germ Cells
  • Oocytes / metabolism
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Tyrosine 3-Monooxygenase / chemistry
  • Tyrosine 3-Monooxygenase / genetics
  • Tyrosine 3-Monooxygenase / metabolism*

Substances

  • 14-3-3 Proteins
  • Caenorhabditis elegans Proteins
  • Drosophila Proteins
  • par-5 protein, C elegans
  • Tyrosine 3-Monooxygenase
  • Protein-Serine-Threonine Kinases